This Phase 1 SBIR application is for preparation of protocol and vaccine for a randomized, placebo-controlled, double-blind, multicenter Phase II clinical trial of an antibody-inducing trivalent vaccine against neuroblastoma. Its foundation is 3 years of studies during which time 1) vaccine design for optimal antibody responses against defined cancer cell surface antigens was determined to include chemical conjugation of antigen to carrier molecule keyhole limpet hemocyanin (KLH) and administration with the saponin immunological adjuvant QS-21 (our QS- 21 is termed OPT-821), 2) the benefit of immunization in the minimal disease setting where circulating tumor cells, micrometastases and partially treated metastases are the primary targets was demonstrated in preclinical studies and this benefit was shown to be magnified by oral co- administration of beta-glucan, 3) the antigens expressed by the common cancers were defined and 3 antigens most relevant for a neuroblastoma vaccine identified as GD2, GD3 and polysialic acid, 4) the safety and immunogenicity of monovalent and polyvalent vaccines against these three antigens was confirmed and the optimal dose of each conjugate and adjuvant in patients in the post-chemotherapy adjuvant setting determined, and 5) the safety, immunogenicity and optimal dose in neuroblastoma patients of a vaccine containing GD2, GD3 and OPT-821 co- administered with beta-glucan were demonstrated. The primary endpoints of the proposed randomized Phase II trial (that would be addressed in a subsequent Phase 2 SBIR application) are prolongation of disease-free and overall survival of second or third complete response stage 4 neuroblastoma patients vaccinated with the full trivalent vaccine compared to those vaccinated with OPT-821 alone. Under this Phase 1 application, the protocol will be IRB approved, the vaccines prepared and the IND for this vaccine and placebo obtained. PUBLIC HEALTH RELEVANCE: Project Narrative Antibodies induced by the trivalent vaccine (GD2, GD3 and polysialic acid) proposed here against neuroblastoma cell surface antigens are ideally suited for eradication of circulating neuroblastoma cells, micrometastasis and partially-treated metastases. If antibodies of sufficient titer can be induced against these antigens to eliminate tumor cells from the blood and to eradicate early metastasis, this would dramatically change our approach to treating the neuroblastoma patient. Establishment of new metastasis would no longer be possible so treatment with chemotherapy might result in long-term control of even metastatic neuroblastoma.